Iron(II)-catalyzed asymmetric intramolecular aminohydroxylation of indoles

Article abstract of DOI:10.1021/ol401666e

An enantioselective intramolecular indole aminohydroxylation reaction is catalyzed by iron(II)-chiral bisoxazoline (BOX) complexes (ee up to 99%, dr > 20:1). This discovery enables expedient asymmetric synthesis of a series of biologically active 3-amino

Full text of DOI:10.1021/ol401666e

ORGANIC
LETTERS
2013
Vol. 15, No. 15
3910–3913
Iron(II)-Catalyzed Asymmetric
Intramolecular Aminohydroxylation
of Indoles
Yong-Qiang Zhang, Yong-An Yuan, Guan-Sai Liu, and Hao Xu*
Department of Chemistry, Georgia State University, 100 Piedmont Avenue SE, Atlanta,
Georgia 30303, United States
hxu@gsu.edu
Received June 12, 2013
ABSTRACT
An enantioselective intramolecular indole aminohydroxylation reaction is catalyzed by iron(II)ꢀchiral bisoxazoline (BOX) complexes (ee up to 99%, dr > 20:1).
This discovery enables expedient asymmetric synthesis of a series of biologically active 3-amino oxindoles and 3-amino indolanes.
Both amino oxindoles and amino indolanes are struc-
tural motifs present in numerous medicinal agents and
biologically active natural products, such as AG-041R, a
gastrin/CCK-B receptor agonist, SSR-149415, a medicine
for the treatment of anxiety and depression,1 and natural
products psychotrimine, kapakahines, and chaetomin.2
Therefore, extensive research effort has been devoted to
development of methods for enantioselective synthesis of
amino oxindoles and amino indolanes. Chiral substrate-
controlled indoleꢀaniline coupling and stereospecific
functional group manipulation are among the strategies
that have been applied to the asymmetric synthesis of
3-amino indolanes;2c,d however, strategies based on asym-
metric catalysis still remain highly desirable. There recently
has been exciting progress in catalytic asymmetric synthesis of
3-amino oxindoles including (a) organic molecules and Lewis
acid-catalyzed addition of oxindoles to azodicarboxylates;3
(4) (a) Jia, Y.-X.; Hillgren, J. M.; Watson, E. L.; Marsden, S. P.;
€
Kundig, E. P. Chem. Commun. 2008, 4040. (b) Tolstoy, P.; Lee, S. X. Y.;
Sparr, C.; Ley, S. V. Org. Lett. 2012, 14, 4810.
(5) Hara, N.; Nakamura, S.; Sano, M.; Tamura, R.; Funahashi, Y.;
Shibata, N. Chem.;Eur. J. 2012, 18, 9276.
(6) (a) Sharpless, K. B.; Chong, A. O.; Oshima, K. J. Org. Chem.
1976, 41, 177. (b) Li, G. G.; Chang, H. T.; Sharpless, K. B. Angew.
Chem., Int. Ed. 1996, 35, 451.
(1) (a) Ochi, M.; Kawasaki, K.; Kataoka, H.; Uchio, Y.; Nishi, H.
Biochem. Biophys. Res. Commun. 2001, 283, 1118. (b) Bernard, K.;
Bogliolo, S.; Ehrenfeld, J. Br. J. Pharmacol. 2005, 144, 1037.
(2) For selected references of isolation and synthesis of 3-aminoin-
dolane natural products, see: (a) Takayama, H.; Mori, I.; Kitajima, M.;
Aimi, N.; Lajis, N. H. Org. Lett. 2004, 6, 2945. (b) Matsuda, Y.;
Kitajima, M.; Takayama, H. Org. Lett. 2007, 10, 125. (c) Newhouse,
T.; Baran, P. S. J. Am. Chem. Soc. 2008, 130, 10886. (d) Espejo, V. R.;
Rainier, J. D. J. Am. Chem. Soc. 2008, 130, 12894. (e) Takahashi, N.; Ito,
T.; Matsuda, Y.; Kogure, N.; Kitajima, M.; Takayama, H. Chem.
Commun. 2010, 2501.
€
(7) (a) Noack, M.; Gottlich, R. Chem. Commun. 2002, 536. (b)
Michaelis, D. J.; Shaffer, C. J.; Yoon, T. P. J. Am. Chem. Soc. 2007,
129, 1866. (c) Michaelis, D. J.; Ischay, M. A.; Yoon, T. P. J. Am. Chem.
Soc. 2008, 130, 6610. (d) Benkovics, T.; Du, J.; Guzei, I. A.; Yoon, T. P.
J. Org. Chem. 2009, 74, 5545. (e) Michaelis, D. J.; Williamson, K. S.;
Yoon, T. P. Tetrahedron 2009, 65, 5118. (f) Fuller, P. H.; Kim, J.-W.;
Chemler, S. R. J. Am. Chem. Soc. 2008, 130, 17638. (g) Paderes, M. C.;
Chemler, S. R. Org. Lett. 2009, 11, 1915. (h) Sherman, E. S.; Chemler,
S. R. Adv. Synth. Catal. 2009, 351, 467. (i) Mancheno, D. E.; Thornton,
A. R.; Stoll, A. H.; Kong, A.; Blakey, S. B. Org. Lett. 2010, 12, 4110. (j)
Alexanian, E. J.; Lee, C.; Sorensen, E. J. J. Am. Chem. Soc. 2005, 127,
7690. (k) Liu, G.; Stahl, S. S. J. Am. Chem. Soc. 2006, 128, 7179. (l)
Desai, L. V.; Sanford, M. S. Angew. Chem., Int. Ed. 2007, 46, 5737. (m)
Schmidt, V. A.; Alexanian, E. J. J. Am. Chem. Soc. 2011, 133, 11402. (n)
Xu, H.-C.; Moeller, K. D. J. Am. Chem. Soc. 2008, 130, 13542. (o)
Donohoe, T. J.; Johnson, P. D.; Cowley, A.; Keenan, M. J. Am. Chem.
Soc. 2002, 124, 12934. (p) Donohoe, T. J.; Callens, C. K. A.; Flores, A.;
(3) (a) Cheng, L.; Liu, L.; Wang, D.; Chen, Y.-J. Org. Lett. 2009, 11,
3874. (b) Bui, T.; Borregan, M.; Barbas, C. F., III. J. Org. Chem. 2009,
ꢀ
74, 8935. (c) Bui, T.; Hernandez-Torres, G.; Milite, C.; Barbas, C. F.
Org. Lett. 2010, 12, 5696. (d) Mouri, S.; Chen, Z.; Mitsunuma, H.;
Furutachi, M.; Matsunaga, S.; Shibasaki, M. J. Am. Chem. Soc. 2010,
132, 1255. (e) Yang, Z.; Wang, Z.; Bai, S.; Shen, K.; Chen, D.; Liu, X.;
Lin, L.; Feng, X. Chem.;Eur. J. 2010, 16, 6632. (f) Shen, K.; Liu, X.;
Wang, G.; Lin, L.; Feng, X. Angew. Chem., Int. Ed. 2011, 50, 4684. (g)
Shen, K.; Liu, X.; Lin, L.; Feng, X. Chem. Sci. 2012, 3, 327. (h) Liu, X.;
Lin, L.; Feng, X. Acc. Chem. Res. 2011, 44, 574.
~
Lacy, A. R.; Rathi, A. H. Chem.;Eur. J. 2011, 17, 58. (q) Muniz, K.;
Iglesias, A.; Fang, Y. Chem. Commun. 2009, 5591. (r) de Haro, T.;
Nevado, C. Angew. Chem., Int. Ed. 2011, 50, 906.
r
10.1021/ol401666e
Published on Web 07/22/2013
2013 American Chemical Society

(b) intramolecular R-arylation of amides;4 and (c) organic
molecule-catalyzed addition to isatin-derived ketoimines.5
Despite these key discoveries, a method that can provide
both amino oxindoles and amino indolanes with synthetically
useful ee through catalytic asymmetric indole aminohydrox-
ylation has yet to be discovered.
Scheme 1. Iron(II)-Catalyzed Intramolecular Aminohydroxy-
lation of Olefins and Indoles
Inspired by the pioneering Sharpless asymmetric
aminohydroxylation,6 there has been significant progress
in the development of methods for selective olefin
aminohydroxylation.7 Nonetheless, direct aminohydrox-
ylation of indoles has largely remained unexplored, with a
few exceptions: Padwa, Che, Du Bois, and Iwabuchi
independently reported rhodium-catalyzed intramolecular
aminohydroxylation of indoles or pyrroles;8 Yoon discov-
ered a copper-catalyzed intermolecular indole aminohydrox-
ylation with oxaziridines;9 and Dauban disclosed a rhodium-
catalyzed intermolecular indole aminohydroxylation.10 De-
spite these important achievements, the catalytic asymmetric
aminohydroxylation of indoles with synthetically useful ee
has remained a challenge.11 Likewise, iron-catalyzed olefin
aminohydroxylation is also a less-explored process;12 how-
ever, Yoon recently discovered an iron-catalyzed olefin
aminohydroxylation with sulfonyl oxaziridines.13 We have
recently reported an iron-catalyzed intramolecular olefin
aminohydroxylation and the mechanistic studies revealed
that an iron-nitrenoid is a possible intermediate in the
selective atom transfer reaction (Scheme 1A).14 Herein, we
describe our latest discovery: an iron(II)-catalyzed asym-
metric intramolecular aminohydroxylation of indoles. In this
reaction, the iron catalyst diastereo- and enantioselectively
transfers the N and O groups of the hydroxylamine to a
variety of indoles (dr > 20:1, ee up to 99%). Simple product
derivatization provides both amino oxindoles and amino
indolanes in their enantioenriched forms (Scheme 1B).
We initiated the catalyst discovery with a model sub-
strate 1 and extensive optimization revealed that the
FeSO4ꢀ1,10-phenanthroline complex catalyzes an effi-
cient racemic indole aminohydroxylation reaction afford-
ing product 2 as a single diastereomer (Scheme 2).15
Scheme 2. Iron(II)-Catalyzed Racemic Intramolecular Indole
Aminohydroxylation
With the optimized racemic reaction in hand, we set out
to search for chiral ligands that effectively promote en-
antioselective indole aminohydroxylation with iron(II)
complexes (Table 1). Since FeSO4 is poorly soluble in
nonpolar solvents such as toluene, we selected Fe(OTf)2
as the iron salt for chiral ligand discovery. Extensive
experimentation revealed that a tolueneꢀMeCN (50:1)
mixture is crucial for high enantioselectivity.16 Under these
conditions, we systematically inspected a series of chiral
bisoxazoline (BOX and PyBOX) and pyridineꢀoxazoline
hybrid ligands.17
(8) (a) Padwa, A.; Stengel, T. Org. Lett. 2002, 4, 2137. (b) Mulcahy,
J. V.; Du Bois, J. J. Am. Chem. Soc. 2008, 130, 12630. (c) Sato, S.;
Shibuya, M.; Kanoh, N.; Iwabuchi, Y. Chem. Commun. 2009, 6264. (d)
Liang, J.-L.; Yuan, S.-X.; Chan, P. W. H.; Che, C.-M. Tetrahedron Lett.
2003, 44, 5917.
(9) Benkovics, T.; Guzei, I. A.; Yoon, T. P. Angew. Chem., Int. Ed.
2010, 49, 9153.
(10) Beaumont, S.; Pons, V.; Retailleau, P.; Dodd, R. H.; Dauban, P.
Angew. Chem., Int. Ed. 2010, 49, 1634.
(11) The previously reported best ee of indole aminohydroxylation is
i
53%; see ref 8d.
We observed that the Fe(OTf)2ꢀ PrBOX L1 complex
(12) For selected reviews of iron-catalyzed reactions in organic
synthesis, see: (a) Bolm, C.; Legros, J.; Le Paih, J.; Zani, L. Chem.
Rev. 2004, 104, 6217. (b) Enthaler, S.; Junge, K.; Beller, M. Angew.
fails to induce any enantioselectivity (entry 1); however, the
€
Chem., Int. Ed. 2008, 47, 3317. (c) Sherry, B. D.; Fuerstner, A. Acc.
(15) For catalyst optimization in details, see the Supporting Informa-
tion. The relative stereochemistry of the product was determined by
X-ray crystallographic analysis.
(16) This is the optimized result from the screening. A decreased ee
was observed in toluene. See the Supporting Information for tempera-
ture, solvent, and concentration optimization in details.
Chem. Res. 2008, 41, 1500. For selected examples of iron-catalyzed
asymmetric oxidation reactions, see: (d) Collman, J. P.; Wang, Z.;
Straumanis, A.; Quelquejeu, M.; Rose, E. J. Am. Chem. Soc. 1999,
121, 460. (e) Gelalcha, F. G.; Bitterlich, B.; Anilkumar, G.; Tse, M. K.;
Beller, M. Angew. Chem., Int. Ed. 2007, 46, 7293. (f) Suzuki, K.;
Oldenburg, P. D.; Que, L. Angew. Chem., Int. Ed. 2008, 47, 1887. (g)
Egami, H.; Matsumoto, K.; Oguma, T.; Kunisu, T.; Katsuki, T. J. Am.
Chem. Soc. 2010, 132, 13633. (h) Nishikawa, Y.; Yamamoto, H. J. Am.
Chem. Soc. 2011, 133, 8432. (i) Zhu, S. F.; Cai, Y.; Mao, H. X.; Xie, J. H.;
Zhou, Q. L. Nat. Chem. 2010, 2, 546.
(13) (a) Williamson, K. S.; Yoon, T. P. J. Am. Chem. Soc. 2010, 132,
4570. (b) Williamson, K. S.; Yoon, T. P. J. Am. Chem. Soc. 2012, 134,
12370.
(14) Liu, G.-S.; Zhang, Y.-Q.; Yuan, Y.-A.; Xu, H. J. Am. Chem.
Soc. 2013, 135, 3343.
(17) For selected leading references and reviews of chiral bisoxazoline
ligands in asymmetric catalysis, see: (a) Corey, E. J.; Imai, N.; Zhang,
H. Y. J. Am. Chem. Soc. 1991, 113, 728. (b) Evans, D. A.; Faul, M. M.;
Bilodeau, M. T.; Anderson, B. A.; Barnes, D. M. J. Am. Chem. Soc.
1993, 115, 5328. (c) Pfaltz, A. Acc. Chem. Res. 1993, 26, 339. (d)
Desimoni, G.; Faita, G.; Jørgensen, K. A. Chem. Rev. 2006, 106, 3561.
ꢀ
ꢀ
(e) Malkov, A. V.; Liddon, A. J. P. S.; Ramırez-Lopez, P.; Bendova, L.;
ꢁ
ꢀ
Haigh, D.; Kocovsky, P. Angew. Chem., Int. Ed. 2006, 45, 1432. (f)
Stokes, B. J.; Opra, S. M.; Sigman, M. S. J. Am. Chem. Soc. 2012, 134,
11408.
Org. Lett., Vol. 15, No. 15, 2013
3911

tuning experiments on the benzoyl protecting group. We
discovered that the 4-Cl, 4-CF3, and 3,5-(CF3)2 substitu-
ents result in decreased ee while the 4-CO2Me group
maintains the similar ee (entries 11ꢀ14 compared with
entry 9). We also observed that hydrolytically more robust
Fe(NTf2)220 promotes thereactionwithaslightlyincreased
yield yet decreased ee (entry 15, 67% yield, 79% ee).
Concordantly, we discovered that both FeCl2 and FeBr2
promote less selective reactions with L9 (entries 16ꢀ17);
however, the Fe(OAc)2ꢀL9 complex manages to increase
the ee to 90% in 12 h (entry 18).
Table 1. Catalyst Discovery for Iron(II)-Catalyzed Asymmetric
Indole Aminohydroxylation
In order to search for a more reactive yet highly selective
catalyst, we inspected a variety of additives with bulky
N-donor ability.21 Extensive optimization revealed that 2,6-
lutidine (1.0 equiv) significantly accelerates the Fe(OTf2)ꢀL9
catalyzed reaction in toluene with a slight increase in en-
antioselectivity (Scheme 3, full conversion in 45 min at
ꢀ10 °C, 65% yield, 88% ee). This discovery offers us an
opportunity to expand substrate scope and include substrates
that have low reactivity in Fe(OAc)2-catalyzed reactions.
entrya
Fe(X)2
ligand
R0
yieldb (%) eec (%)
1
Fe(OTf)2
Fe(OTf)2
Fe(OTf)2
Fe(OTf)2
Fe(OTf)2
Fe(OTf)2
Fe(OTf)2
Fe(OTf)2
Fe(OTf)2
Fe(OTf)2
Fe(OTf)2
Fe(OTf)2
Fe(OTf)2
Fe(OTf)2
L1
L2
L3
L4
L5
L6
L7
L8
L9
2,4-Cl2-benzoyl
2,4-Cl2-benzoyl
2,4-Cl2-benzoyl
2,4-Cl2-benzoyl
2,4-Cl2-benzoyl
2,4-Cl2-benzoyl
2,4-Cl2-benzoyl
2,4-Cl2-benzoyl
2,4-Cl2-benzoyl
22
25
58
48
15
33
21
25
65
50
62
65
58
75
67
63
52
67
0
31
77
ꢀ86
32
22
37
61
87
81
87
77
78
75
79
86
75
90
2
3
4d
5
6
Scheme 3. Iron(II)-Catalyzed Indole Aminohydroxylation
Accelerated by 2,6-Lutidine
7
8
9
10
11
12
13
14
15
16
17
18
L10 2,4-Cl2-benzoyl
L9
L9
L9
L9
4-CO2-Me-benzoyl
4-CF3-benzoyl
4-Cl-benzoyl
3,5-(CF3)2-benzoyl
2,4-Cl2-benzoyl
2,4-Cl2-benzoyl
2,4-Cl2-benzoyl
2,4-Cl2-benzoyl
Fe(NTf2)2 L9
FeCl2
L9
L9
L9
FeBr2
To explore the scope and limitation of the aforemen-
tioned method, we applied the optimized reaction condi-
tions to a variety of substituted indoles (Table 2). We
observed that 5-methylindole is an excellent substrate for
Fe(OAc)2-catalyzed asymmetric aminohydroxylation (AA)
(entry 2, 94% ee). Likewise, the Fe(OTf)2ꢀL9ꢀlutidine
complex enantioselectively converts a 5-methoxy indole to
its corresponding hydroxyl oxazolidinone (entry 3, 93% ee).
We also discovered that 6-methyl-, bromo-, and chloro-
substituents are all well-tolerated in the Fe(OAc)2-catalyzed
indole AA, which thereby offers versatile handles for further
transformation (entries 4ꢀ6, 91ꢀ99% ee). Further explora-
tion revealed that 6-phenyl indole is an excellent substrate
for Fe(OTf)2-catalyzed AA (entry 7, 91% ee) and that
7-methyl indole participates in the Fe(OAc)2-catalyzed
AA with acceptable ee (entry 8, 88% ee). However, we
observed that the ee for aminohydroxylation of 4-bromo
indole is significantly lower than other substrates
(entry 9, 74% ee), which suggests that 4-H may be important
for asymmetric induction.
Fe(OAc)2
a Reactions were carried out under argon in 0.025 M toluene/MeCN
(50:1) mixture; catalyst complexes were formed by premixing Fe(X)2 and
ligands for 40 min. b Isolated yield. c ee was measured by HPLC analysis
with chiral stationary phase. d The sense of enantioinduction in entry 4 is
the opposite to that of other entries.
t
Fe(OTf)2ꢀ BuBOX L2 complex is capable of asymmetric
induction (entry 2, 31% ee). The change from L2 to PhBOX
L3 correlates with both enhanced reactivity and enantios-
electivity (entry 3, 58% yield, 77% ee).18 Surprisingly, a
relatively minor modification to the ligand’s structure (from
PhBOX L3 to BnBOX L4) leads to asymmetric induction in
the opposite sense (entry 4, 48% yield, ꢀ86% ee). We there-
fore tested PyBOX and pyridine-oxazoline hybrid ligands
L5ꢀL8 and determined that they are inferior to L3 and L4
(entries 5ꢀ8, ee up to 61%). Further screening of tetrasub-
stituted chiral BOX ligands (L9ꢀL10) revealed that the Fe-
(OTf)2ꢀL9 complex catalyzes the indole aminohydroxylation
with further enhanced ee (entry 9, 65% yield, 87% ee).
Knowing that aromatic interactions may be important
for asymmetric induction,19 we carried out electronic
The enantio-enriched hydroxyl oxazolidinone 2 can be
readily converted to either amino indolane 3 or amino
(20) Fe(NTf2)2 was prepared in aqueous solvent. For its preparation,
see: Sibi, M. P.; Petrovic, G. Tetrahedron: Asymmetry 2003, 14, 2879.
(21) For the effect of additives with bulky N-donor ability in iron-
catalyzed oxidation reactions, see: (a) Lee, D.; Lippard, S. J. J. Am.
Chem. Soc. 1998, 120, 12153. (b) Hagadorn, J. R.; Que, L.; Tolman,
W. B. J. Am. Chem. Soc. 1998, 120, 13531.
(18) The absolute stereochemistry of the product was determined by
X-ray crystallographic analysis; see the Supporting Information for
details.
(19) Knowles, R. R.; Jacobsen, E. N. Proc. Natl. Acad. Sci. U.S.A.
2010, 107, 20678.
3912
Org. Lett., Vol. 15, No. 15, 2013

Table 2. Substrate Scope for the Iron(II)-Catalyzed Asymmetric
Intramolecular Aminohydroxylation of Indoles
Scheme 4. Synthetic Transformation of the Product and the
Iron(II)-Catalyzed Aminohydroxylation of Tryptophan
entrya
R
yieldb (%)
eec (%)
1
H
67
72
75
65
64
70
65
62
67
90
94
93
95
91
99
91
85
74
2d
3d,e
4
5-Me
5-OMe
6-Me
6-Br
5
6
6-Cl
7e
8d
9
7-Ph
7-Me
4-Br
a Reactions were carried out under argon in 0.025 M toluene/MeCN
(50:1) mixture, unless stated otherwise. b Isolated yield, and 3-indole
aldehydes were isolated (ca. 15%) as the side product. c ee was measured
by HPLC analysis with chiral stationary phase. d R1 = 4-CO2Me-
benzoyl. e Reactions were carried out under argon at 0.025 M toluene
at ꢀ10 °C for 4 h. Fe(OTf)2 (15 mol %) and L9 (30 mol %) were applied
as the catalyst and 2,6-lutidine (1.0 equiv) was used as the additive.
oxindole 4 without erosion of the ee with three-step proce-
dures(Scheme4A).TheN-sulfonyl protected amino oxindole
motif is of interest in medicinal chemistry because it is present
in SSR-149415, a medicine for the treatment of anxiety and
depression.1 In order to develop an easy entry to both
unprotected amino indolanes and oxindoles, we explored
the aminohydroxylation of an N-Boc protected indole 5
(Scheme 4B). We observed that Fe(OAc)2ꢀL9 complex
catalyzes the efficient aminohydroxylation of 5 with an even
lower catalyst loading, affording product 6 with excellent
yield (10 mol % catalyst, 85% yield, dr > 20:1, 87% ee).22
We further observed that the Fe(NTf2)2ꢀphenanthroline
complex catalyzes the aminohydroxylation of a protected
tryptophan 7 to afford a single diastereomeric hydroxyl
oxazolidinone 8 (full conversion, 46% yield, Scheme 4C);
interestingly, the aminohydroxylation occurs from the R
face of tryptophan.23 In addition, we also isolated diazeti-
dinone 9 (25% yield), a side product that is possibly derived
from an NꢀH insertion reaction of the putative iron-
nitrenoid intermediate.24 We therefore applied the same
catalyst to another fully protected tryptophan 10 and ob-
served the efficient aminohydroxylation to afford 11.25
In conclusion, we have discovered an asymmetric intra-
molecular indole aminohydroxylation catalyzed by iron-
(II)ꢀchiral BOX complexes. This enantioselective process
enables the facile asymmetric synthesis of biologically
relevant 3-amino oxindoles and 3-amino indolanes. Our
current research focuses on the application of this method
in medicinal agent synthesis and better understanding of
the origin for asymmetric induction.
Acknowledgment. This work was supported by Georgia
State University and the American Chemical Society
Petroleum Research Fund (ACS PRF 51571-DNI1).
(22) The protected hydroxyl oxazolidinone 6 has been converted to
the unprotected amino indolane and oxindole follwing the same proce-
dure. See the Supporting Information for details.
(23) The absolute stereochemistry of the product was determined by
X-ray crystallographic analysis; see the Supporting Information for
details.
(24) When either Fe(NTf2)2ꢀL9 or Fe(NTf2)2ꢀent-L9 was applied as
the catalyst, we only isolated diazetidinone 9 (78ꢀ81% yield); see the
Supporting Information for details.
(25) Fe(NTf2)2ꢀL9 and Fe(NTf2)2ꢀent-L9 are less-efficient catalysts
to afford 11: 37ꢀ43% yield, 1.0ꢀ1.2 dr at the C2 position. The low yield
of 11 is due to starting material 10 decomposition. We did not observe
significant rate difference with different handed chiral catalysts. See the
Supporting Information for details.
Supporting Information Available. Experimental pro-
cedure, characterization data for all new compounds, selected
NMR spectra, HPLC traces, and X-ray crystallographic
analysis data are available. This material is available free of
charge via the Internet at http://pubs.acs.org.
The authors declare no competing financial interest.
Org. Lett., Vol. 15, No. 15, 2013
3913